The objectives of the proposed research are to investigate the rheological behavior of red blood cell (RBC) and white blood cell (WBC) membranes, to study the interactions of these membranes with the environment, to study the role of blood cell properties in circulatory regulation, and to correlate these functions with the molecular organization of RBC membranes, both in health and in blood diseases. The rheology of normal and abnormal RBC and WBC membranes during deformation at constant area and during area stretching (including hemolysis) will be experimentally studied, modeled by theoretical computation, and correlated with membrane structure determined by ultra-structural and cytochemical methods. The mechanism of membrane transport of hexoses will be studied in RBC ghosts, and the transport process will be correlated with the molecular organization of RBC membranes determined by cytochemical methods. The expression of i-I antigens on the exoface of sickle cell membrane will be correlated with the cell content of Hb F. The forces involved in the interaction of the membrane exoface with macromolecules (including abnormal plasma proteins) will be studied experimentally, and the micromechanics of cell aggregation will be modeled theoretically. The role of altered blood cell properties in affecting blood flow dynamics and metabolic transport will be studied in the macrocirculation and the microcirculation. The ultimate aim of the research is to provide the fundamental knowledge needed for improving the diagnosis and treatment of hematological diseases.